Caveolin-1 Controls Hyperresponsiveness to Mechanical Stimuli and Fibrogenesis-Associated RUNX2 Activation in Keloid Fibroblasts

Chao Kai Hsu, Hsi Hui Lin, Hans I. Harn, Rei Ogawa, Yang Kao Wang, Yen Ting Ho, Wan Rung Chen, Yi Chao Lee, Julia Yu Yun Lee, Shyh Jou Shieh, Chao Min Cheng, John A. McGrath, Ming Jer Tang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Keloids are pathological scars characterized by excessive extracellular matrix production that are prone to form in body sites with increased skin tension. CAV1, the principal coat protein of caveolae, has been associated with the regulation of cell mechanics, including cell softening and loss of stiffness sensing ability in NIH3T3 fibroblasts. Although CAV1 is present in low amounts in keloid fibroblasts (KFs), the causal association between CAV1 down-regulation and its aberrant responses to mechanical stimuli remain unclear. In this study, atomic force microscopy showed that KFs were softer than normal fibroblasts with a loss of stiffness sensing. The decrease of CAV1 contributed to the hyperactivation of fibrogenesis-associated RUNX2, a transcription factor germane to osteogenesis/chondrogenesis, and increased migratory ability in KFs. Treatment of KFs with trichostatin A, which increased the acetylation level of histone H3, increased CAV1 and decreased RUNX2 and fibronectin. Trichostatin A treatment also resulted in cell stiffening and decreased migratory ability in KFs. Collectively, these results suggest a role for CAV1 down-regulation in linking the aberrant responsiveness to mechanical stimulation and extracellular matrix accumulation with the progression of keloids, findings that may lead to new developments in the prevention and treatment of keloid scarring.

Original languageEnglish
Pages (from-to)208-218
Number of pages11
JournalJournal of Investigative Dermatology
Volume138
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Caveolin 1
Keloid
Fibroblasts
Chemical activation
trichostatin A
Cicatrix
Extracellular Matrix
Stiffness
Down-Regulation
Acetylation
Chondrogenesis
Caveolae
Capsid Proteins
Atomic Force Microscopy
Fibronectins
Histones
Mechanics
Osteogenesis
Atomic force microscopy
Skin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Caveolin-1 Controls Hyperresponsiveness to Mechanical Stimuli and Fibrogenesis-Associated RUNX2 Activation in Keloid Fibroblasts. / Hsu, Chao Kai; Lin, Hsi Hui; Harn, Hans I.; Ogawa, Rei; Wang, Yang Kao; Ho, Yen Ting; Chen, Wan Rung; Lee, Yi Chao; Lee, Julia Yu Yun; Shieh, Shyh Jou; Cheng, Chao Min; McGrath, John A.; Tang, Ming Jer.

In: Journal of Investigative Dermatology, Vol. 138, No. 1, 01.01.2018, p. 208-218.

Research output: Contribution to journalArticle

Hsu, CK, Lin, HH, Harn, HI, Ogawa, R, Wang, YK, Ho, YT, Chen, WR, Lee, YC, Lee, JYY, Shieh, SJ, Cheng, CM, McGrath, JA & Tang, MJ 2018, 'Caveolin-1 Controls Hyperresponsiveness to Mechanical Stimuli and Fibrogenesis-Associated RUNX2 Activation in Keloid Fibroblasts', Journal of Investigative Dermatology, vol. 138, no. 1, pp. 208-218. https://doi.org/10.1016/j.jid.2017.05.041
Hsu, Chao Kai ; Lin, Hsi Hui ; Harn, Hans I. ; Ogawa, Rei ; Wang, Yang Kao ; Ho, Yen Ting ; Chen, Wan Rung ; Lee, Yi Chao ; Lee, Julia Yu Yun ; Shieh, Shyh Jou ; Cheng, Chao Min ; McGrath, John A. ; Tang, Ming Jer. / Caveolin-1 Controls Hyperresponsiveness to Mechanical Stimuli and Fibrogenesis-Associated RUNX2 Activation in Keloid Fibroblasts. In: Journal of Investigative Dermatology. 2018 ; Vol. 138, No. 1. pp. 208-218.
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